Investigations are concerned with the oxidation of arachidonic acid to prostaglandins (PG), leukotrienes and hydroxy-fatty acids and the relationship of this metabolism to the regulation or modulation of biological processes. Human airway calls were found not biosynthesize PGs but to make 15-HPETE and its metabolites. Arachidonic acid metabolism by porcine alveolar and intravascular macrophages is very different with intravascular more active than alveolar. We have also investigated the mechanism responsible for the inhibition of PHS by phenylbutazone (Pb). Pb must be oxidized by PHS peroxidase for inhibition to occur. Pb- peroxide was not a substrate for PHS peroxidase nor an inhibitor. The data indicates that Pb alkoxyl or peroxyl radicals are responsible for the inhibition. We have also investigated the role of arachidonic acid metabolism in mitogenesis. Mouse B lymphocytes oxidized arachidonic acid to 12-HPETE and 12-HETE. Inhibitors of 12- lipoxgenase inhibit lipopolysaccharide (LPS) dependent mitogenesis. The addition of cofactors for peroxidase inhibited mitogenesis without altering the total oxidation of arachidonic acid. A new arachidonic acid metabolite produced by lymphocytes has been isolated characterized as a mixture of 19/20 hydroxy-12-HETE with one or more double bond reduced. Further studies are required to determine the position and extent of reduction. We have also studied arachidonic acid metabolism and EGF induced mitogenesis in BALBc 3T3 cells. EGF induces the formation of PGE2 (the major arachidonic acid metabolite) and mitogenesis. Indomethacin, dexamethasone, and NDGA block PGE2 formation and mitogenesis. Prostaglandins are weakly mitogenic but the addition of PGs to indomethacin inhibited EGF-stimulated mitogenesis restored DNA synthesis. Moreover, the addition of PGs greatly enhance EGF mitogenesis. These studies suggest a possible important role for arachidonic acid metabolism in regulating cell growth.